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Mefenamic Acid is indicated for-

• Fever
• Toothache
• Headache
• Migraine
• Primary dysmenorrhoea
• Menorrhagia
• Mild to moderate pain in rheumatoid arthritis and osteoarthritis
• Traumatic pain
• Low-back pain
• Juvenile chronic arthritis in children etc.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Mefenamic acid contains Mefenamic Acid which is a nonsteroidal agent with demonstrated analgesic, anti-inflammatory and antipyretic activity due to its dual action on prostaglandins. It inhibits the enzymes of prostaglandin synthetase and also antagonizes the actions of prostaglandin at the receptor sites.

Adult:

• 500 mg dose should be given to adults upto three times (1.5 gm total) per day with meals. The dosage may be reduced to 1 tablet (250 mg) three times daily.
• In case of menorrhagia: 500 mg three times daily with meals and from the onset of menses and continued according to the judgement of the physician.

Children:

• 6 months to 1 year: 5 ml three times/day.
• 2-4 years: 10 ml three times/day.
• 5-8 years: 10 ml four times /day.
• 9-12 years: 15 ml four times/day.

Treatment should not be continued for more than 7 days except on the advice of a physician.

The most frequently reported adverse experiences occurring in approximately 1-10% of patients are gastrointestinal: abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea, Gl ulcers, vomiting, dizziness, abnormal renal function, pruritus, rashes.

It is contraindicated in patients with known hypersensitivity to Mefenamic Acid. It should not be used in patients with peptic ulcer, inflammatory bowel diseases, hepatic or renal impairment. It is also contraindicated in patients, whom aspirin and/or other NSAID's have induced symptoms of bronchospasm, skin rashes etc.

It should be administered with caution in allergic diseases especially in asthma. The treatment should be withdrawn in diarrhoea, rashes, cholestatic jaundice, thrombocytopenia, haemolytic anaemia.

Aspirin: As other NSAIDs, concomitant administration of Mefenamic Acid and Aspirin is not generally recommended because of the potential of increased adverse effects.

Warfarin: Mefenamic Acid can inhibit platelet aggregation and may prolong the prothrombin time in patients on warfarin therapy

The safety of Mefenamic acid on reproductive capacity and pregnancy has not been established. Thus, mefenamic acid should be used in women of childbearing potential and during pregnancy only when the potential benefits are expected to outweigh the potential risks. Trace amounts of Mefenamic acid may be present in breast milk and transmitted to the nursing infant. Thus Mefenamic acid should not be taken by the nursing mother because of the effects of this class of drugs on the infant's cardiovascular system.

Keep away from light, store in a cool and dry place. Keep out of reach of children.

Mefenamic Acid is indicated for-

• Fever
• Toothache
• Headache
• Migraine
• Primary dysmenorrhoea
• Menorrhagia
• Mild to moderate pain in rheumatoid arthritis and osteoarthritis
• Traumatic pain
• Low-back pain
• Juvenile chronic arthritis in children etc.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Mefenamic acid contains Mefenamic Acid which is a nonsteroidal agent with demonstrated analgesic, anti-inflammatory and antipyretic activity due to its dual action on prostaglandins. It inhibits the enzymes of prostaglandin synthetase and also antagonizes the actions of prostaglandin at the receptor sites.

Adult:

• 500 mg dose should be given to adults upto three times (1.5 gm total) per day with meals. The dosage may be reduced to 1 tablet (250 mg) three times daily.
• In case of menorrhagia: 500 mg three times daily with meals and from the onset of menses and continued according to the judgement of the physician.

Children:

• 6 months to 1 year: 5 ml three times/day.
• 2-4 years: 10 ml three times/day.
• 5-8 years: 10 ml four times /day.
• 9-12 years: 15 ml four times/day.

Treatment should not be continued for more than 7 days except on the advice of a physician.

The most frequently reported adverse experiences occurring in approximately 1-10% of patients are gastrointestinal: abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea, Gl ulcers, vomiting, dizziness, abnormal renal function, pruritus, rashes.

It is contraindicated in patients with known hypersensitivity to Mefenamic Acid. It should not be used in patients with peptic ulcer, inflammatory bowel diseases, hepatic or renal impairment. It is also contraindicated in patients, whom aspirin and/or other NSAID's have induced symptoms of bronchospasm, skin rashes etc.

It should be administered with caution in allergic diseases especially in asthma. The treatment should be withdrawn in diarrhoea, rashes, cholestatic jaundice, thrombocytopenia, haemolytic anaemia.

Aspirin: As other NSAIDs, concomitant administration of Mefenamic Acid and Aspirin is not generally recommended because of the potential of increased adverse effects.

Warfarin: Mefenamic Acid can inhibit platelet aggregation and may prolong the prothrombin time in patients on warfarin therapy

The safety of Mefenamic acid on reproductive capacity and pregnancy has not been established. Thus, mefenamic acid should be used in women of childbearing potential and during pregnancy only when the potential benefits are expected to outweigh the potential risks. Trace amounts of Mefenamic acid may be present in breast milk and transmitted to the nursing infant. Thus Mefenamic acid should not be taken by the nursing mother because of the effects of this class of drugs on the infant's cardiovascular system.

Keep away from light, store in a cool and dry place. Keep out of reach of children.

Mefenamic Acid is indicated for-

• Fever
• Toothache
• Headache
• Migraine
• Primary dysmenorrhoea
• Menorrhagia
• Mild to moderate pain in rheumatoid arthritis and osteoarthritis
• Traumatic pain
• Low-back pain
• Juvenile chronic arthritis in children etc.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Mefenamic acid contains Mefenamic Acid which is a nonsteroidal agent with demonstrated analgesic, anti-inflammatory and antipyretic activity due to its dual action on prostaglandins. It inhibits the enzymes of prostaglandin synthetase and also antagonizes the actions of prostaglandin at the receptor sites.

Adult:

• 500 mg dose should be given to adults upto three times (1.5 gm total) per day with meals. The dosage may be reduced to 1 tablet (250 mg) three times daily.
• In case of menorrhagia: 500 mg three times daily with meals and from the onset of menses and continued according to the judgement of the physician.

Children:

• 6 months to 1 year: 5 ml three times/day.
• 2-4 years: 10 ml three times/day.
• 5-8 years: 10 ml four times /day.
• 9-12 years: 15 ml four times/day.

Treatment should not be continued for more than 7 days except on the advice of a physician.

The most frequently reported adverse experiences occurring in approximately 1-10% of patients are gastrointestinal: abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea, Gl ulcers, vomiting, dizziness, abnormal renal function, pruritus, rashes.

It is contraindicated in patients with known hypersensitivity to Mefenamic Acid. It should not be used in patients with peptic ulcer, inflammatory bowel diseases, hepatic or renal impairment. It is also contraindicated in patients, whom aspirin and/or other NSAID's have induced symptoms of bronchospasm, skin rashes etc.

It should be administered with caution in allergic diseases especially in asthma. The treatment should be withdrawn in diarrhoea, rashes, cholestatic jaundice, thrombocytopenia, haemolytic anaemia.

Aspirin: As other NSAIDs, concomitant administration of Mefenamic Acid and Aspirin is not generally recommended because of the potential of increased adverse effects.

Warfarin: Mefenamic Acid can inhibit platelet aggregation and may prolong the prothrombin time in patients on warfarin therapy

The safety of Mefenamic acid on reproductive capacity and pregnancy has not been established. Thus, mefenamic acid should be used in women of childbearing potential and during pregnancy only when the potential benefits are expected to outweigh the potential risks. Trace amounts of Mefenamic acid may be present in breast milk and transmitted to the nursing infant. Thus Mefenamic acid should not be taken by the nursing mother because of the effects of this class of drugs on the infant's cardiovascular system.

Keep away from light, store in a cool and dry place. Keep out of reach of children.

Mefenamic Acid is indicated for-

• Fever
• Toothache
• Headache
• Migraine
• Primary dysmenorrhoea
• Menorrhagia
• Mild to moderate pain in rheumatoid arthritis and osteoarthritis
• Traumatic pain
• Low-back pain
• Juvenile chronic arthritis in children etc.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Mefenamic acid contains Mefenamic Acid which is a nonsteroidal agent with demonstrated analgesic, anti-inflammatory and antipyretic activity due to its dual action on prostaglandins. It inhibits the enzymes of prostaglandin synthetase and also antagonizes the actions of prostaglandin at the receptor sites.

Adult:

• 500 mg dose should be given to adults upto three times (1.5 gm total) per day with meals. The dosage may be reduced to 1 tablet (250 mg) three times daily.
• In case of menorrhagia: 500 mg three times daily with meals and from the onset of menses and continued according to the judgement of the physician.

Children:

• 6 months to 1 year: 5 ml three times/day.
• 2-4 years: 10 ml three times/day.
• 5-8 years: 10 ml four times /day.
• 9-12 years: 15 ml four times/day.

Treatment should not be continued for more than 7 days except on the advice of a physician.

The most frequently reported adverse experiences occurring in approximately 1-10% of patients are gastrointestinal: abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea, Gl ulcers, vomiting, dizziness, abnormal renal function, pruritus, rashes.

It is contraindicated in patients with known hypersensitivity to Mefenamic Acid. It should not be used in patients with peptic ulcer, inflammatory bowel diseases, hepatic or renal impairment. It is also contraindicated in patients, whom aspirin and/or other NSAID's have induced symptoms of bronchospasm, skin rashes etc.

It should be administered with caution in allergic diseases especially in asthma. The treatment should be withdrawn in diarrhoea, rashes, cholestatic jaundice, thrombocytopenia, haemolytic anaemia.

Aspirin: As other NSAIDs, concomitant administration of Mefenamic Acid and Aspirin is not generally recommended because of the potential of increased adverse effects.

Warfarin: Mefenamic Acid can inhibit platelet aggregation and may prolong the prothrombin time in patients on warfarin therapy

The safety of Mefenamic acid on reproductive capacity and pregnancy has not been established. Thus, mefenamic acid should be used in women of childbearing potential and during pregnancy only when the potential benefits are expected to outweigh the potential risks. Trace amounts of Mefenamic acid may be present in breast milk and transmitted to the nursing infant. Thus Mefenamic acid should not be taken by the nursing mother because of the effects of this class of drugs on the infant's cardiovascular system.

Keep away from light, store in a cool and dry place. Keep out of reach of children.

Mefenamic Acid is indicated for-

• Fever
• Toothache
• Headache
• Migraine
• Primary dysmenorrhoea
• Menorrhagia
• Mild to moderate pain in rheumatoid arthritis and osteoarthritis
• Traumatic pain
• Low-back pain
• Juvenile chronic arthritis in children etc.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Mefenamic acid contains Mefenamic Acid which is a nonsteroidal agent with demonstrated analgesic, anti-inflammatory and antipyretic activity due to its dual action on prostaglandins. It inhibits the enzymes of prostaglandin synthetase and also antagonizes the actions of prostaglandin at the receptor sites.

Adult:

• 500 mg dose should be given to adults upto three times (1.5 gm total) per day with meals. The dosage may be reduced to 1 tablet (250 mg) three times daily.
• In case of menorrhagia: 500 mg three times daily with meals and from the onset of menses and continued according to the judgement of the physician.

Children:

• 6 months to 1 year: 5 ml three times/day.
• 2-4 years: 10 ml three times/day.
• 5-8 years: 10 ml four times /day.
• 9-12 years: 15 ml four times/day.

Treatment should not be continued for more than 7 days except on the advice of a physician.

The most frequently reported adverse experiences occurring in approximately 1-10% of patients are gastrointestinal: abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea, Gl ulcers, vomiting, dizziness, abnormal renal function, pruritus, rashes.

It is contraindicated in patients with known hypersensitivity to Mefenamic Acid. It should not be used in patients with peptic ulcer, inflammatory bowel diseases, hepatic or renal impairment. It is also contraindicated in patients, whom aspirin and/or other NSAID's have induced symptoms of bronchospasm, skin rashes etc.

It should be administered with caution in allergic diseases especially in asthma. The treatment should be withdrawn in diarrhoea, rashes, cholestatic jaundice, thrombocytopenia, haemolytic anaemia.

Aspirin: As other NSAIDs, concomitant administration of Mefenamic Acid and Aspirin is not generally recommended because of the potential of increased adverse effects.

Warfarin: Mefenamic Acid can inhibit platelet aggregation and may prolong the prothrombin time in patients on warfarin therapy

The safety of Mefenamic acid on reproductive capacity and pregnancy has not been established. Thus, mefenamic acid should be used in women of childbearing potential and during pregnancy only when the potential benefits are expected to outweigh the potential risks. Trace amounts of Mefenamic acid may be present in breast milk and transmitted to the nursing infant. Thus Mefenamic acid should not be taken by the nursing mother because of the effects of this class of drugs on the infant's cardiovascular system.

Keep away from light, store in a cool and dry place. Keep out of reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Lomefloxacin ophthalmic preparation is indicated in the bacterial infections, including conjunctivitis, blepharitis, blepharoconjunctivitis which are due to Lomefloxacin susceptible germs and Staphylococcus aureus- induced corneal ulcers.

4-Quinolone preparations, Ophthalmic antibacterial drugs

Lomefloxacin, a difluorinated quinolone derivative, is a bacterial gyrase inhibitor, effective against gram positive and gram negative bacteria. The acute toxicity of Lomefloxacin following systemic and topical ophthalmic application is low. Lomefloxacin interferes with bacterial DNA related processes like initiation, elongation, and termination phases of replication, transcription, DNA repairing, recombination, transposition, supercoiling and relaxation of DNA. The target molecule for quinolones is the A-subunit of bacterial enzyme gyrase (topoisomerase II). The forming of a stable complex between the quinolone and the whole gyrase teramer A2B2 leads to impaired enzyme functions, resulting in a rapid killing of sensitive bacteria.

Cross-resistance has only been reported with other quinolones, but not with any other group of antibiotics. No clinical studies are available about the efficacy in cases of infections with chlamydia.

Adults and children (above 1 year of age): Instill 2-3 times daily 1 drop into the lower conjunctival sac. At the beginning of the treatment application should be more frequent, apply 5 drops within 20 minutes or 1 drop every hour during 6-10 hours. Duration of the treatment: 7 to 9 days.

May be taken with or without food.

Slight and transient burning immediately after instillation of the eye drops has been reported in 4.7% of users. Although phototoxicity has not been reported after ophthalmic use, photosensitization is possible. Since the following allergic reactions have been reported after systemic use of Lomefloxacin, they can not be excluded after topical ophthalmic use: allergic reactions, asthma, dyspnoea, urticaria, erythema, pruritus, and hypersensitization.

Hypersensitivity to the active ingredient, to excipients, or to quinolones. Long term treatment with antibiotics may enhance development of secondary fungal infections or may support growth of non susceptible bacteria.

Some isolated cases of phototoxicity have been reported after systemic but not after topical ophthalmic use of Lomefloxacin. Nevertheless, during treatment with Lomefloxacin intensive exposure to sunlight or UV-radiation should be avoided

In order to avoid reduction of efficacy, no ophthalmic preparations containing heavy metals, such as zinc, should be used during 15 minutes preceding and following application of Lomefloxacin. Bacteriostatic ophthalmic antibiotics should not be used concomitantly with Lomefloxacin eye drops.

Animal studies revealed that after systemic use of 20 mg/kg, Lomefloxacin passes the placenta barrier and is excreted into the maternal milk. Clinical studies on the use of Lomefloxacin eye drops during human pregnancy or lactation are not available. Therefore, the drug should only be used when the benefit outweighs the potential risk for the foetus or the infant.

Practically there is no risk of adverse effects due to accidental oral ingestion, since a bottle of 5 ml eye drop solution contains only 15 mg Lomefloxacin. This corresponds to 3.75% of the recommended oral daily dose for adults of 400 mg Lomefloxacin.

Store at 15-25° C

Mefloquine is indicated in-

• Acute Malaria Infections caused by Mefloquine-susceptible strains of Plasmodium falciparum (both chloroquine- susceptible and resistant strains) or by P. vivax
• Prophylaxis of P. falciparum and P. vivax malaria infections

Anti-malarial drugs

Mefloquine has been found to produce swelling of the Plasmodium falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components.

Mefloquine is an antimalarial agent which acts as a blood schizonticide. Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Mefloquine is a chiral molecule. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.

Adult:

• Malaria prevention: 1 tablet (250 mg) once per week starting 1-2 weeks before departure and continued for 4 weeks after leaving malarious area.
• Malaria treatment: 5 tablets (5X250 mg) in a single dose (up to max. 1.5 gm) or preferably in 2 divided doses 6 to 8 hours apart.

In Children 6 Months and Older:

• Malaria prevention: Approximately 5 mg/kg body weight once per week (250 mg for children weighing over 45 kg, decreasing in proportion to body weight for children weighing 45 kg or less).
• Malaria treatment: 20 to 25 mg/kg body weight which may be split into two doses 6 to 8 hours apart to reduce the occurrence or severity of adverse reactions.

Geriatric Use: Experiences have not identified differences in responses between the elderly and younger patients.

Should be taken with food. Best taken with meals & a full glass of water.

Among subjects who received Mefloquine for prophylaxis of malaria, following side effects was observed:

• The most frequently observed sied-effects were vomiting, dizziness, syncope, extrasystoles and other complaints affecting less than 1%. Among subjects who received Mefloquine for treatment, following side-effects was observed:
• The most frequently observed side-effects included : dizziness, myalgia, nausea, fever, headache, vomiting, chills, diarrhoea, skin rash, abdominal pain fatigue, loss of appetite, and tinnitus

Use of Mefloquine is contraindicated in patients with a known hypersensitivity to Mefloquine or related compounds (e.g. quinine and quinidine). It should not be prescribed for prophylaxis in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders, or with a history of convulsions.

Warnings: Mefloquine may cause psychiatric symptoms in a number of patients, ranging from anxiety, paranoia, and depression to hallucinations and psychotic behavior. Rare cases of suicidal ideation and suicide have been reported though no relationship to drug administration has been confirmed. Mefloquine should be used with caution in patients with a previous history of depression. Concomitant administration of Mefloquine and quinine or quinidine may produce electrocardiographic abnormalities and may increase risk of convulsions.

Precautions: In patients with epilepsy, Mefloquine may increase the risk of convulsions. Caution should be exercised with regard to activities requiring alertness and fine motor coordination such as driving, piloting aircraft and operating machinery. Mefloquine should be used with caution in patients with psychiatric disturbances. In patients with impaired liver function the elimination of Mefloquine may be prolonged, leading to higher plasma levels.

Increased risk of ECG abnormalities with quinine or chloroquine, antihistamines, TCAs and phenothiazines. May increase risk of seizure with quinidine or quinine. Concomitant use with valproic acid, phenobarbital, carbamazepine and phenytoin may cause loss of seizure control and lower plasma levels of anticonvulsants. Increased risk of QT prolongation and arrhythmia with ketoconazole. Concomitant use with digoxin, Ca channel blockers, antiarrhythmics and β-blockers may increase the risk of cardiotoxicity. Increased risk of ventricular arrhythmias with amiodarone. Concomitant use with TCAs, SSRIs, buprion, antipsychotic, tramadol may increase the risk of convulsions. Increased plasma levels with metoclopromide. May compromise adequate immunisation by live typhoid vaccine. Vaccinations with attenuated live bacteria should be completed at least 3 days prior the 1st dose of mefloquine.

Use in Pregnancy: There is no adequate and well-controlled study in pregnant women. However, clinical experience with Mefloquine has not revealed an embrytoxic or teratogenic effect. Mefloquine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in Nursing Mothers: Mefloquine is excreted in breast milk in small amounts. the activity of which is unknown. Because of the potential for serious adverse reactions in nursing infants form Mefloquine. a decision should be made whether to discontinue the drug taking into account the importance of the drug to the mother.

In cases of overdosage with Mefloquine, the symptoms may be more pronounced. The following procedure is recommended in case of overdosage:

• Induce vomiting or perform gastric lavage, as appropriate.
• Monitor cardiac function (if possible by ECG), neurologic and psychiatric status for at least 24 hours.
• Provide Symptomatic and intensive supportive treatment as required, particularly of cardiovascular disturbance.
• Treat vomiting or diarrhoea with standard fluid therapy.

Store in a cool dry place. Protect from light.

Combination Oral hypoglycemic preparations

Metformin is a biguanide antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacological mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylurea, metformin does not produce hypoglycemia in either patient with type 2 diabetes or normal subjects and does not cause hyperinsulinemia.

Glipizide is a sulfonylurea which appears to lower blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.

Glipizide & Metformin should be given once or twice daily with meals and should be initiated at a low dose, with gradual dose escalation.

Glipizide & Metformin as Initial Therapy: The recommended starting dose is 250 mg/2.5 mg once a day with meal.

Glipizide & Metformin as Second-Line Therapy: The recommended starting dose is 500 mg/2.5 mg or 500 mg/5 mg twice daily with the morning and evening meals. The maximum recommended daily dose is 2000 mg Metformin/20 mg Glipizide.

The most common side effects of Glipizide & Metformin are hypoglycemia,
diarrhea, nausea/vomiting, abdominal pain, headache, musculoskeletal pain etc.

Hypersensitivity to the drug, renal impairment, diabetic coma and ketoacidosis, chronic renal diseases, congestive heart failure, trauma, dehydration, alcohol dependence, pregnancy, breast-feeding etc.

Metformin is known to be substantially excreted by the kidney, and the risk of Metformin accumulation and lactic acidosis is increased with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal should not receive Metformin. In patients with advanced age, Metformin should be carefully titrated to establish minimum dose for adequate glycemic control, because aging is associated with reduced renal function. Metformin therapy should be temporarily suspended for any surgical procedure and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal. During concomitant therapy with sulfonylurea, blood glucose should be monitored. Metformin & insulin therapy should be carried out in hospital until the correct ratio of the two drugs has been established. The metabolism and excretion of Glipizide may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.

Cimetidine reduces the renal clearance of Metformin. Alcohol potentiates the antihyperglycemic & hyperlactataemic effect of Metformin. It may enhance the effects of anti-coagulants. Such patients receiving the two drugs may need adjustment of the anti-coagulant dosage. Nifedipine appears to enhance the absorption of Metformin but Metformin has minimal effects on Nifedipine. The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents.

Contraindicated during Pregnancy & Lactation

Store below 25ºC in a cool and dry place.

Combination Oral hypoglycemic preparations

Metformin is a biguanide antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacological mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylurea, metformin does not produce hypoglycemia in either patient with type 2 diabetes or normal subjects and does not cause hyperinsulinemia.

Glipizide is a sulfonylurea which appears to lower blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.

Glipizide & Metformin should be given once or twice daily with meals and should be initiated at a low dose, with gradual dose escalation.

Glipizide & Metformin as Initial Therapy: The recommended starting dose is 250 mg/2.5 mg once a day with meal.

Glipizide & Metformin as Second-Line Therapy: The recommended starting dose is 500 mg/2.5 mg or 500 mg/5 mg twice daily with the morning and evening meals. The maximum recommended daily dose is 2000 mg Metformin/20 mg Glipizide.

The most common side effects of Glipizide & Metformin are hypoglycemia,
diarrhea, nausea/vomiting, abdominal pain, headache, musculoskeletal pain etc.

Hypersensitivity to the drug, renal impairment, diabetic coma and ketoacidosis, chronic renal diseases, congestive heart failure, trauma, dehydration, alcohol dependence, pregnancy, breast-feeding etc.

Metformin is known to be substantially excreted by the kidney, and the risk of Metformin accumulation and lactic acidosis is increased with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal should not receive Metformin. In patients with advanced age, Metformin should be carefully titrated to establish minimum dose for adequate glycemic control, because aging is associated with reduced renal function. Metformin therapy should be temporarily suspended for any surgical procedure and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal. During concomitant therapy with sulfonylurea, blood glucose should be monitored. Metformin & insulin therapy should be carried out in hospital until the correct ratio of the two drugs has been established. The metabolism and excretion of Glipizide may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.

Cimetidine reduces the renal clearance of Metformin. Alcohol potentiates the antihyperglycemic & hyperlactataemic effect of Metformin. It may enhance the effects of anti-coagulants. Such patients receiving the two drugs may need adjustment of the anti-coagulant dosage. Nifedipine appears to enhance the absorption of Metformin but Metformin has minimal effects on Nifedipine. The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents.

Contraindicated during Pregnancy & Lactation

Store below 25ºC in a cool and dry place.

Combination Oral hypoglycemic preparations

Metformin is a biguanide antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacological mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylurea, metformin does not produce hypoglycemia in either patient with type 2 diabetes or normal subjects and does not cause hyperinsulinemia.

Glipizide is a sulfonylurea which appears to lower blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.

Glipizide & Metformin should be given once or twice daily with meals and should be initiated at a low dose, with gradual dose escalation.

Glipizide & Metformin as Initial Therapy: The recommended starting dose is 250 mg/2.5 mg once a day with meal.

Glipizide & Metformin as Second-Line Therapy: The recommended starting dose is 500 mg/2.5 mg or 500 mg/5 mg twice daily with the morning and evening meals. The maximum recommended daily dose is 2000 mg Metformin/20 mg Glipizide.

The most common side effects of Glipizide & Metformin are hypoglycemia,
diarrhea, nausea/vomiting, abdominal pain, headache, musculoskeletal pain etc.

Hypersensitivity to the drug, renal impairment, diabetic coma and ketoacidosis, chronic renal diseases, congestive heart failure, trauma, dehydration, alcohol dependence, pregnancy, breast-feeding etc.

Metformin is known to be substantially excreted by the kidney, and the risk of Metformin accumulation and lactic acidosis is increased with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal should not receive Metformin. In patients with advanced age, Metformin should be carefully titrated to establish minimum dose for adequate glycemic control, because aging is associated with reduced renal function. Metformin therapy should be temporarily suspended for any surgical procedure and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal. During concomitant therapy with sulfonylurea, blood glucose should be monitored. Metformin & insulin therapy should be carried out in hospital until the correct ratio of the two drugs has been established. The metabolism and excretion of Glipizide may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.

Cimetidine reduces the renal clearance of Metformin. Alcohol potentiates the antihyperglycemic & hyperlactataemic effect of Metformin. It may enhance the effects of anti-coagulants. Such patients receiving the two drugs may need adjustment of the anti-coagulant dosage. Nifedipine appears to enhance the absorption of Metformin but Metformin has minimal effects on Nifedipine. The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents.

Contraindicated during Pregnancy & Lactation

Store below 25ºC in a cool and dry place.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Mefenamic Acid is indicated for-

• Fever
• Toothache
• Headache
• Migraine
• Primary dysmenorrhoea
• Menorrhagia
• Mild to moderate pain in rheumatoid arthritis and osteoarthritis
• Traumatic pain
• Low-back pain
• Juvenile chronic arthritis in children etc.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Mefenamic acid contains Mefenamic Acid which is a nonsteroidal agent with demonstrated analgesic, anti-inflammatory and antipyretic activity due to its dual action on prostaglandins. It inhibits the enzymes of prostaglandin synthetase and also antagonizes the actions of prostaglandin at the receptor sites.

Adult:

• 500 mg dose should be given to adults upto three times (1.5 gm total) per day with meals. The dosage may be reduced to 1 tablet (250 mg) three times daily.
• In case of menorrhagia: 500 mg three times daily with meals and from the onset of menses and continued according to the judgement of the physician.

Children:

• 6 months to 1 year: 5 ml three times/day.
• 2-4 years: 10 ml three times/day.
• 5-8 years: 10 ml four times /day.
• 9-12 years: 15 ml four times/day.

Treatment should not be continued for more than 7 days except on the advice of a physician.

The most frequently reported adverse experiences occurring in approximately 1-10% of patients are gastrointestinal: abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea, Gl ulcers, vomiting, dizziness, abnormal renal function, pruritus, rashes.

It is contraindicated in patients with known hypersensitivity to Mefenamic Acid. It should not be used in patients with peptic ulcer, inflammatory bowel diseases, hepatic or renal impairment. It is also contraindicated in patients, whom aspirin and/or other NSAID's have induced symptoms of bronchospasm, skin rashes etc.

It should be administered with caution in allergic diseases especially in asthma. The treatment should be withdrawn in diarrhoea, rashes, cholestatic jaundice, thrombocytopenia, haemolytic anaemia.

Aspirin: As other NSAIDs, concomitant administration of Mefenamic Acid and Aspirin is not generally recommended because of the potential of increased adverse effects.

Warfarin: Mefenamic Acid can inhibit platelet aggregation and may prolong the prothrombin time in patients on warfarin therapy

The safety of Mefenamic acid on reproductive capacity and pregnancy has not been established. Thus, mefenamic acid should be used in women of childbearing potential and during pregnancy only when the potential benefits are expected to outweigh the potential risks. Trace amounts of Mefenamic acid may be present in breast milk and transmitted to the nursing infant. Thus Mefenamic acid should not be taken by the nursing mother because of the effects of this class of drugs on the infant's cardiovascular system.

Keep away from light, store in a cool and dry place. Keep out of reach of children.

First generation Cephalosporins

Cephradine is a semisynthetic broad spectrum bactericidal antibiotic, it is active against infections caused by both gram-positive and gram-negative microorganisms. Both penicillinase producing and nonproducing staphylococci are sensitive to Cephradine. The main site of action of Cephradine is the cell wall of bacteria. Cell wall of sensitive organism contains peptidoglycan. Cephradine inhibits cross-linking process and as a result cell wall with many pores are formed, thus lysis of bacteria occur due to external osmotic pressure.

For oral administration-
Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly: The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration-

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Limited essentially to gastro-intestinal disturbances and on occasions to hypersensitivity phenomena. The latter are more likely to occur in individuals, who have previously demonstrated hypersensitivity and thos with a history of allergy, asthma, hay fever or urticaria. Skin reactions have occasionally been reported. Rare- Glossitis, heartburn, dizziness, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, vaginitis, candida overgrowth. Skin and hypersensitivity reactions include urticaria, skin rashes, joint pains, oedema.

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Cephradine should not be used in patients with known or suspected hypersensitivity to cephalosporins.

The concomitant use of nephrotoxic drugs such as aminoglycosides with Cefradine may increase the risk of kidney damage. Diuretics (e.g. frusemide, ethacrynic acid) and probenecid enhanced the possibility of renal toxicity.

Although animal studies have not demonstrated any teratogenicity, safety in pregnancy has not been established. Cephradine is excreted in breast milk and should be used with caution in lactating mothers. Since the medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Renal Impairment: The following doses are recommended (based on 500 mg every 6 hours) for patients not on haemodialysis:

• CrCl: >20 ml/min: 500 mg every 6 hours
• CrCl: 5-20 ml/min: 250 mg every 6 hours
• CrCl: <5 ml/min: 250 mg every 50-70 hours.

Recommendations for patients on chronic, intermittent haemodialysis:

• 250 mg at the start of haemodialysis
• 250 mg 6 to 12 hours after the start
• 250 mg 36 to 48 hours after the start
• 250 mg at the start of the next haemodialysis session if more than 30 hours have elapsed since the last dose.

Additional Information for all patients Regardless of patient age or weight, higher doses of up to 1 gm four times daily may be required for infections which are chronic or severe. Treatment should continue for at least 2 to 3 days after symptoms have resolved or bacteria have been eradicated. To reduce the possibility of rheumatic fever or glomerulonephritis resulting from infections with haemolytic streptococci, treatment should be continued for at least 10 days. Throughout treatment of chronic urinary tract infections and for several months thereafter, regular bacteriological and clinical monitoring is required.

Doses below those recommended above should not be prescribed. Paediatric dosages should not exceed those specified for adults, regardless of severity of infection. It may be necessary to continue Cephradine therapy for several weeks in persistent infections. Patients may be transferred from intramuscular/intravenous Cephradine therapy to oral treatment at the same dosage level.

The symptoms of Sefrad overdose are non-specific and are generally nausea, vomiting, diarrhoea and gastric upsets. Treatment is mainly supportive although gastric lavage will be necessary if a large amount has been ingested.

Cephradine Suspension should be freshly prepared. Reconstituted Suspension should be used within 7 days if kept at room temperature or within 14 days, if kept in a refrigerator. Cephradine Injection solutions should be used within 2 hours when kept at room temperature. When stored at 5°C, solutions retain potency for 12 hours. Reconstituted solutions may vary in colour from light to straw yellow; however, this does not affect the potency. Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician